Effect of DL111-IT on progesterone biosynthesis and viability of rat luteal cells in vitro  

作　　者：杨波[1,2] 曹霖[1,2] 方瑞英 顾芝萍[1,2] 

机构地区：[1]中国科学院上海药物研究所 [2]浙江医科大学药学系药理教研室

出　　处：《中国药理学报》1997年第4期361-370,共10页Acta Pharmacologica Sinica

摘　　要：目的：研究抗孕唑（ＤＬ１１１ＩＴ）对离体大鼠黄体细胞孕酮合成和存活率的影响．方法：体外培养大鼠黄体细胞，用细胞计数和放射免疫法．结果：ＤＬ１１１ＩＴ使黄体细胞存活率随剂量上升而下降，ＥＤ５０为７７（７１－８５）ｍｇ·Ｌ－１．ＤＬ１１１ＩＴ３ｍｇ·Ｌ－１使黄体细胞基础黄体酮分泌下降２５％，并可显著抑制弗司扣林（ｃＡＭＰ激动剂）１０μｍｏｌ·Ｌ－１和孕烯醇酮（可被３βＨＳＤ催化成黄体酮）１０μｍｏｌ·Ｌ－１的促孕酮分泌作用，抑制率分别为４３％和１５５％，但不抑制ｈＣＧ１０ＩＵ·Ｌ－１的促黄体酮分泌作用．结论：ＤＬ１１１ＩＴ抗早孕作用是在ｃＡＭＰ和３βＨＳＤ水平上影响基础黄体酮分泌功能，并于高剂量降低黄体细胞成活率．IM: To study the influence of DL111 IT on progesterone biosynthesis of cultured luteal cells (LC). METHODS: LC viability was assessed with trypan blue dye exclusion and progesterone concentration was measured with radio￣immuno￣assay. RESULTS: DL111 IT decreased the viability of LC after 24 h incubation, its ED 50 being 7 7 (95 % confidence limits: 7 1-8 5) mg·L -1 . DL111 IT inhibited basal secretion of progesterone in a concentration dependent manner, and 3 mg ·L -1 decreased progesterone concentration by 25 % vs control. DL111 IT 3 mg·L -1 also inhibited the stimulatory effect of forskolin (cAMP activator) 10 μmol·L -1 and pregnenolone [converted to proges￣ter￣one by 3β hydroxysteroid dehydrogenase isomerase complex (3β HSD)] 10 μmol·L -1 on progesterone production in cultured LC, and their inhibitory rates were 43 % and 155 % , respec￣tively. At the same concentration, DL111 IT did not influence hCG induced progesterone production. CONCLUSION: DL111 IT inhibited progesterone synthesis by suppressing the conversion of pregnenolone to progesterone (inactivating 3β HSD) and suppressed the activity of cAMP. DL111 IT 6-24 mg·L -1 decreased the viability of LC.

关 键 词：抗孕唑 黄体 黄体酮 细胞存活 生物合成 

分 类 号：R979.21[医药卫生—药品]